Nephrology Hypertension

Medical Management of the Dialysis Patient: Nutritional Assessment and Support

Is this patient malnourished?

Malnutrition is an important issue in dialysis patients because it can lead to suboptimal health and, in certain circumstances, even frank illness. Moreover, dialysis patients are particularly predisposed to malnutrition because of a combination of underlying disease states, frequent advanced age, lower socioeconomic status and education levels, and the effects of uremia.

Dialysis treatment itself may also contribute to the risk of malnutrition. While metabolism does not appear to be different between dialysis patients and healthy individuals, the hemodialysis procedure leads to protein breakdown and total body and muscle protein loss. There is also concern over protein loss with peritoneal dialysis, especially in the setting of peritonitis.

Because of differences in how malnutrition is defined, there is great confusion over its diagnosis and management. The World Health Organization (WHO) defines malnutrition clearly and precisely as “inadequate or excess intake of protein, energy, and micronutrients such as vitamins, and the frequent infections and disorders that result.” This definition presumes that malnutrition can be overcome simply by altering the composition of the diet. Of note, malnutrition can involve macronutrients (fat, carbohydrates, protein), micronutrients (vitamins, minerals), or a combination of the two. The WHO definition should be used as the standard definition of what constitutes malnutrition in dialysis patients.

An expert panel convened by the International Society of Renal Nutrition and Metabolism (ISRNM) recently addressed the overlapping syndromes of malnutrition, inflammation, cachexia, and wasting. They defined protein-energy wasting as the state of decreased body stores of protein and energy fuels, and cachexia as a severe form of protein-energy wasting. However, these definitions are not as clinically useful as the WHO definition in terms of identifying malnutrition because they do not address abnormalities in micronutrient intake or excess protein/calorie intake, nor do they limit the causes of protein and energy wasting to nutrition-related ones.

While the malnutrition of uremia traditionally presents with loss of lean body mass and a gaunt, wasted appearance, the most common form of malnutrition in the contemporary dialysis population is probably overnutrition, as manifested by overweight and obesity. The average body mass index for the US dialysis population has risen progressively over the past two decades and now approaches the obesity range.

Malnutrition remains primarily a clinical, rather than laboratory, diagnosis. In most instances, clinical context and index of suspicion, not laboratory testing, are key to making the diagnosis. Hence, the diagnosis will be most dependent upon elements in the medical and nutritional history and physical exam, though laboratory findings may contribute.

The principal components of the nutritional assessment include the history and physical exam (Table I). The history should include questions about medical conditions that may affect dietary intake, absorption, or metabolism; the composition of the patient’s diet; and symptoms that are suggestive of malnutrition. A dietary evaluation should also address whether the patient adheres to extreme or fad diets, has specific food intolerances, and uses medications that may inhibit gastrointestinal absorption. A thorough dietary history can be facilitated with the assistance of a dietician/nutritional consultant.

Inadequate protein or calorie intake leading to loss of lean body mass is perhaps the state of malnutrition most classically associated with uremia and dialysis. However, this can be a misleading phenomenon, because lean body mass can also be lost in dialysis patients independent of nutritional intake through changes precipitated by such factors as metabolic acidosis, angiotensin II, insulin resistance, and inflammation, all of which lead via multiple pathways to upregulation of the ATP-dependent ubiquitin-proteasome system (UPS). It is this system that is primarily responsible for degrading protein in skeletal muscle.

The major challenge to clinicians in establishing the diagnosis of malnutrition in dialysis patients is distinguishing between true protein-calorie deficiency malnutrition that is amenable to nutritional interventions versus the effects of inflammatory and related conditions that are not affected by nutritional intake. However, both malnutrition and inflammatory wasting may exist in a single patient, and it is often very difficult to tease apart these processes diagnostically. Both can present with weight loss and reductions in lean body mass (e.g., skeletal muscle), though patients with inflammatory wasting often have preserved or even excess fat mass. Malnutrition is usually associated with minor, if any, reductions in serum albumin, while inflammatory wasting is typically associated with much more severe reductions. Finally, only malnutrition is amenable to nutritional interventions.

If a patient is malnourished as a result of inadequate nutritional intake, then repleting him with the deficient nutrients will correct the problem. This will not be the case with inflammatory wasting. Therefore, the most reliable way to distinguish between the two processes is to treat the patient as if he had malnutrition and see whether he improves. If it fails to correct than an underlying inflammatory state likely exists. Table III summarizes the differences between protein-calorie malnutrition and inflammatory wasting:

Table III.

Protein-Calorie Malnutrition

Inflammatory Wasting

Weight Loss

+++

+ to +++

Physical Signs of Loss of Lean Mass

+++

+/- to +++

Reductions in Serum Albumin

+/-

+++

Improvement with Proper Feeding

+++

+/-

What tests to perform?

There are a number of tools available to assess nutritional status in dialysis patients, including: (1) dietary intake measurements, (2) anthropometric measurements, (3) blood and urine tests, (4) nutritional scoring systems, (5) radiological or electronic-based quantitative measurements. However, because of concerns about the utility, reliability, interpretability, and practicality of these tests, malnutrition remains primarily a clinical diagnosis.

Dietary surveys, including short-term dietary recalls (e.g., 24 hr), longer-term food records (3-7 days) and food frequency questionnaires (FFQs), can be useful in determining the risk of under- or overnutrition. They may also help track changes in dietary intake over time. Of note, all dietary surveys are limited by patient recall and in general underreport energy intake when compared to the gold-standard doubly labelled water technique that measures energy expenditure. Testing should ideally be performed by dieticians or other health professionals trained to administer such surveys.

Anthropometric measurements, including the body mass index (kg/m2), % of standard body weight, triceps skinfold (measures fat), and mid-arm muscle circumference (measures muscle), can be helpful in identifying abnormalities in fat and lean body mass (Table IV). The body mass index is especially easy to calculate in the clinical setting, and while it needs to be placed in the proper clinical context, it can be helpful in identifying changes in nutritional status. Guidelines and data tables on population percentiles of various anthropometric measurements can be found in appendix VII of the 2000 K/DOQI nutrition guidelines (see Clinical Practice Guidelines section). Dietitians are helpful in assisting with these measurements.

Table IV.

BMI (kg/m2)

Category

<18.5

Underweight

18.5 – 24.9

Normal

25 – 29.9

Overweight

30=>

Obese

Serum albumin is the most widely used laboratory marker of nutritional status, perhaps because of its ease of use and interpretation, low cost, and early and strong association with kwashiorkor. In fact, it is routinely used by nephrologists, renal dieticians, federal agencies, health care payors, and large dialysis organizations as a major index of nutrition. The inverse association between serum albumin and mortality is also well known. However, randomized studies in healthy humans and patients with kidney disease strongly suggest that serum albumin does not fall even when protein and/or calories are severely restricted. Moreover, supplementing patients with hypoalbuminemia has not been proven to raise serum albumin. Low serum albumin levels are most often the consequence of an underlying inflammatory disorder, which can reduce hepatic production of albumin and/or increase albumin catabolism and loss of albumin via vascular leakage. Therefore, serum albumin is not a reliable indicator of nutritional status.

Serum prealbumin suffers from the same limitations as albumin.

Similar to albumin and prealbumin, serum cholesterol is an inverse acute phase reactant, so levels will fall in the setting of inflammation. This makes it difficult to interpret in the clinical setting.

Serum creatinine is generated from muscle-derived creatine (and to a lesser extent meat consumption). It may therefore confirm one’s suspicion that a patient has a relative dearth of muscle mass and be used to track lean body mass over time. Similarly, low levels of blood urea nitrogen, which is derived from protein metabolism, may signify poor dietary protein intake.

The Protein Equivalent of Total Nitrogen Appearance (PNA) can help quantify protein intake in dialysis patients. It is based on the fact that in the steady state, protein intake is approximately equivalent to total nitrogen appearance, which itself can be measured by changes in blood urea nitrogen. PNA can be quantified using regression equations described in Appendix V of the 2000 K/DOQI nutrition guidelines.

The Subjective Global Assessment (SGA) is a subjective scoring system commonly used to assess nutritional status via a very focused nutritional history and physical exam that scores nutritional status from 1 (no nutritional loss) to 7 (severe nutritional loss). A dialysis-centric version of the SGA has been developed. While it is a fairly simple and frequently used tool of dieticians, its clinical utility and overall reliability in dialysis patients has been questioned when compared with direct measurement of total body nitrogen, a surrogate for lean body mass.

A number of tools exist to quantitatively measure fat and lean mass in dialysis patients, including bioelectrical impedance analysis (BIA), dual energy x-ray absorptiometry (DXA), and neutron activation analysis. While they can be very useful in the research setting, they are not routinely used in clinical practice because of limitations related to expense, ease of use, and a dearth of information on clinical interpretability.

Table V offers a strategy to focus clinical testing for malnutrition. Tier 1 tests are those that offer maximal information on nutritional status while minimizing complexity and expense. Tier 2 tests offer less information and/or increase complexity and expense, while Tier 3 tests offer the least information and/or are the most expensive or impractical tests. We therefore suggest initiating the clinical workup with Tier 1 tests and moving on to Tier 2 and 3 testing as needed.

Detection of micronutrient deficiencies is not a perfect science. While plasma concentrations may not reflect the availability of micronutrients in the tissues and may not necessarily correspond to functional status, measuring plasma concentrations of micronutrients is generally considered a reasonable way to assess status.

How should malnourished patients be managed?

Treatment of malnutrition in dialysis patients is contingent upon whether 1) the derangement(s) involves macronutrients (e.g. calories, protein, fat) and/or micronutrients (e.g. vitamins, minerals and trace metals), and 2) there is a deficiency or excess of the specific nutrient(s). These derangements can exist independently from one another, so it is possible for a patient to have macronutrient overnutrition (e.g. obesity) and a micronutrient deficiency (e.g. thiamine).

Once the derangements are identified, a proper treatment plan can then be formulated. The next step would be to determine the route of nutrient delivery. In general, the oral or enteric routes take precedence over the parenteral route, in part to prevent mucosal atrophy and loss of the intestinal barrier. As previously mentioned, since it may not always be possible to differentiate true malnutrition from an inflammatory process, it is reasonable to intervene with nutritional supplementation over a discrete period to see if the patient responds.

Mostly opinion-based estimates suggest that daily protein and caloric requirements applicable to the majority of stable peritoneal and hemodialysis patients are greater than that of the general population, though certainly some dialysis patients will be able to consume lower levels without adverse consequences. The National Kidney Foundation K/DOQI Guidelines on daily dietary protein and caloric requirements (Table VI) are a reasonable place to begin in terms of estimating daily requirements.

Protein and/or calorie undernutrition should be treated by supplying the patient with sufficient protein and/or calories to cover both the individual’s daily energy/protein expenditure as well as the deficit itself. In addition, the underlying reason for malnutrition (e.g. depression, dysphagia, etc.) should be treated concomitantly. Of note, because dialysis patients commonly have restrictions in their daily dietary intake of potassium, sodium, phosphorus, and other select nutrients, standard oral or enteral supplements may not be appropriate for use. For example, if hyperkalemia is a concern, supplements containing high concentrations of potassium would be contraindicated.

It is therefore strongly recommended that a dietary prescription be created in collaboration with a dietician or nutrition consultant, if at all possible. If this is not possible then conservative management using renal-tailored prescriptions such as Nepro (oral) or Novasource Renal (enteral) are good options. Table VII and Table VIII describe the contents of commonly used oral and enteral supplements. Of note, oral supplements can also be used as enteral feedings.

Table VII.

Product Name

NeproCarbSteady

Boost

BoostPlus

Resource SF Healthshake

Boost Glucose Control

ResourceBreeze

PeptamenOS

CarnationInstantBreakfast

Flavors

V, ButterPecan

V.C,S

V,C,S

V,C,S

V,C,S

Orange, Peach,Mixed Berry

V,C

V,C,S

Unit

8 oz.

8 oz

8 oz

4 oz.

8 oz.

8 oz.

8 oz.

1 packet

Calories

425

240

360

200

250

250

237

130

Protein(gm/serving)

19

10

14

8

16

9

11.9

5

Carbohydrates(gm/serving)

39

41

45

35

20

54

38.4

28

Fat(gm/serving)

23

4

14

4

12

0

4

1

Na+, mg

250

130

170

125

260

80

250

80

K+, mg

250

400

380

105

260

10

360

312

Calcium, mg

250

300

350

150

276

10

237

250

Phosphorus, mg

170

300

300

150

220

150

237

250

Magnesium, mg

50

100

100

40

80

1

64

80

Osmolarity

585

625

670

n/a

400

750

600

490

Table VIII.

Product Name

Calories/mL

Protein gm/mLProtein-%kcal

Fat gm/LFat-%kcal

Carbs gm/LCHO-%kcal

Na+mEql/L

K+ mEq/L

Phosphorus mEq/L

Calcium mg/L

Magnesium mg/L

mOsm/kg H2O

Free H2O ml/L

Volume for 100% RDI (mL)

Novasource Renal

2

74 15%

100 / 45%

200 / 40%

70

28

650

1300

400

960

709

1000

Isosource HN

1.2

53 / 18%

39 / 29%

160 / 53%

48

49

1200

1200

350

490

818

1165

Fibersource HN

1.2

53 / 18%

39 / 29%

160 / 53%

52

51

1000

1000

350

490

810

1165

Replete

1

62 / 25%

34 / 30%

113 / 45%

38

39

1000

1000

400

300

845

1000

Replete w/Fiber

1

62 / 25%

34 / 30%

113 / 45%

38

39

1000

1000

400

310

835

1000

Crucial

1.5

94 / 25%

68 / 39%

134 / 36%

51

48

1000

1000

400

490

772

1000

Peptamen AF

1.2

76 / 25%

55 / 33%

107 / 36%

35

41

800

800

400

390

811

1500

Peptamen 1.5

1.4

68 / 18%

56 / 33%

188 / 49%

44

48

1000

1000

286

550

771

1000

Glytrol

1

45 / 18%

48 / 42%

100 / 40%

32

36

720

720

200

280

840

1400

Nutren 1.5

1.5

60 / 16%

68 / 39%

169 / 45%

51

48

100

100

430

430

775

1000

Isosource 1.5

1.5

68 / 18%

65 / 38%

170 / 44%

56

58

1070

1070

650

650

778

933

Nutren 2.0

2

80 / 16%

104 / 45%

196 / 39%

57

49

1340

1340

745

745

703

750

In patients who cannot tolerate nutritional feeding via the oral or enteral route, intradialytic parenteral nutrition (IDPN) is an option. This is typically given via a central venous route or dialysis shunt and usually requires the assistance of a nutritional consultant or trained dietician to calculate the appropriate prescription. Of note, the benefits of providing IDPN in the dialysis outpatient setting as supplemental therapy for malnourished patients have not been established. While very short term studies have found that IDPN improves whole-body protein synthesis rates during dialysis, a large randomized study in hemodialysis patients with presumed protein calorie undernutrition found no benefit over oral supplements alone in reducing mortality. Unfortunately, this study probably included patients with inflammatory wasting. The use of IDPN as supplementary therapy in patients who tolerate oral or enteral feedings is therefore not currently recommended.

Other strategies to reverse undernutrition by stimulating appetite with megestrol acetate and ghrelin are in preliminary phases of study. A series of small, mostly nonrandomized trials using oral megestrol suggest that megestrol causes weight gain. The gut hormone ghrelin also stimulates hunger by acting through the hypothalamus. One small randomized study found that subcutaneous ghrelin increased dietary intake in 12 reportedly malnourished dialysis patients for up to 1 week. At this time there is insufficient rigorous evidence to recommend the use of either medication.

The effect of nandrolone decanoate, an anabolic steroid, has been studied for its effect on body composition in healthy hemodialysis patients. While a modestly-sized randomized trial found that nandrolone treatment over 12 weeks increased lean body mass compared with a control group, there are no long term safety or efficacy data using this drug.

Dialysis-related functional deficiencies in L-carnitine, an essential co-factor in fatty acid metabolism, has been linked by some investigators with anemia, intradialytic hypotension, cardiomyopathy, and muscle weakness. However, the use of L-carnitine supplements to treat these disorders is highly controversial. Current recommendations suggest that if used, carnitine supplementation should be tried for limited trial periods and promptly stopped if there is no response.

There is controversy over how to treat dialysis patients with calorie overnutrition who present with overweight or obesity. The problem arises from epidemiological studies that identified a positive relationship between body mass index in dialysis patients and higher rates of survival. However, there are a number of possible alternative explanations for this relationship aside from a causal one.

More recent findings in fact suggest that the relationship between survival and body composition is more complex than was previously realized. Additionally, obesity may adversely influence other important aspects of a patient’s life apart from survival. For example, morbidities such as arthritis that affect quality of life can be worsened by obesity. It is therefore a purely individual clinical decision whether to initiate a weight loss program. If instituted, the patient should be carefully supervised by the nephrologist and a dietician.

Micronutrient deficiencies should be treated in the following manner: If the deficiency is restricted to a single micronutrient, then the patient should be aggressively supplemented with that micronutrient. More often than not, there is concern that dialysis patients may not in general be consuming adequate micronutrients. Because of this and the additional concern that water soluble micronutrients, such as vitamin C and the B vitamins, may be lost in appreciable amounts with hemodialysis, many nephrologists supplement their patients with a daily dialysis “vitamin.” This is a reasonable step, though frank vitamin deficiencies appear to be quite rare in this population, and the benefits of routine supplementation have not been carefully studied. Of note, the optimal daily intake for micronutrients in dialysis patients is not defined. Table IX summarizes the most frequently used prescription dialysis-specific vitamin supplements. There is no evidence that any one is superior to the others.

Table IX.

Ingredient

NephroVite

Nephrocap

Diatx

NephPlex

Dialyvite

Vitamin B1 (thiamine) (mg)

1.5

1.5

1.5

1.5

1.5

Vitamin B2 (riboflavin) (mg)

1.7

1.7

1.5

1.7

1.7

Vitamin B3 (niacin) (mg)

20

20

20

20

20

Vitamin B5 (pantothenic acid) (mg)

10

5

10

10

10

Vitamin B6 (pyridoxine) (mg)

10

10

50

10

10

Vitamin B12 (cyanocobalamin) (mcg or mg)

6 mcg

6 mcg

2 mg

6 mcg

6 mcg

Folic Acid (mg)

0.8

1

5

1

1

Biotin (mcg)

300

150

300

300

300

Vitamin A

—

—

—

—

—

Vitamin C (mg)

60

100

60

60

100

Vitamin D (IU)

—

—

—

—

—

Vitamin E (IU)

—

—

—

—

—

Zinc (mg)

—

—

25

12.5

—

Selenium (mcg)

—

—

—

—

—

Copper (mg)

—

—

1.5

—

—

There are scattered reports of vitamin excesses (i.e. A, C, D) leading to clinical manifestations of hypercalcemia, hyperoxaluria, and neurologic changes. Micronutrient toxicity should be considered when patients report the use of heavy micronutrient supplementation. The treatment is to stop the supplementation.

While there are no nutrition guidelines designed for critically ill hospitalized dialysis patients, two rules should inform one’s treatment strategy. First, the presence of kidney failure in a critically ill patient should never lead to restrictions on nutritional support. For example, severe azotemia will require greater solute clearance, not necessarily cutting back on protein intake. Second, critically ill patients can be highly catabolic, so nutritional intake should be adjusted accordingly. Continuous renal replacement therapy may also contribute to greater protein losses. Nutritional support services and/or dieticians can assist in estimating intake requirements.

What happens to malnourished patients?

Malnutrition has been associated with worse dialysis patient outcomes, including death rates, though causation has yet to be proven.

The exact prevalence and economic impact of malnutrition in dialysis patients is not known. According to DOPPS (Dialysis Outcomes and Practice Patterns Study), the largest international survey of dialysis patients to date, the prevalence of cachexia is between 7.1% and 18.0%, with levels in the U.S. being 9.4%. The potential impact of nutritional intervention on the cost of caring for dialysis patients is also not clearly defined, though some estimates that define malnutrition based on low serum albumin levels suggest that savings would be in the many millions of dollars.

Obesity has become a major nutritional problem in the dialysis population. There is no question that dialysis patients have become increasingly heavier over time. Between 1996 and 2005 the mean body mass index of dialysis patients in the U.S. rose progressively from 25.5 to 28.2 kg/m2. This trend, which reflects changes in the greater society, is unlikely to reverse itself any time soon.

How to utilize team care?

The assessment and management of malnutrition in dialysis patients can be a complex task and a multidisciplinary approach is often required.

Nutrition support services can help with the initial assessment and management prescription, particularly in the inpatient setting. Such teams often contain physician nutrition specialists as well as dieticians.

Gastroenterology consultants may play important roles in assessing pathologic causes of malnutrition and are necessary when endogastric tube placements are required.

Dietitians play a critical role in helping assess the patient’s nutritional state, performing calories counts, and measuring dietary intake. They are also important in providing individualized and family nutritional counseling and following a patient’s progress over time. Fortunately, every outpatient dialysis clinic has dietician support.

Physical therapists can be helpful in detecting swallowing disorders that contribute to malnourished states. They and occupational therapists can also assist in organizing appropriate physical activity in sedentary, obese dialysis patients.

In working to influence the home environment and organizing home nutritional supplementation when necessary, social workers can be an important component of the treatment plan.

Are there clinical practice guidelines to inform decision making?

The 2000 National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF KDOQI) offers an evidence-based clinical practice guideline for malnutrition in dialysis patients. Limitations of the adult guidelines include using a definition of malnutrition that doesn’t differentiate clearly between dietary and inflammatory causes, a lack of information on obesity and micronutrient derangements, and no recent updated version. The children’s guidelines were updated in 2008.

Other clinical practice guidelines available include those from the European Best Practice Guidelines (EBPG) on Nutrition, the European Society of Parenteral and Enteral Nutrition (ESPEN), and the Expert Working Group report on nutrition in adult patients with renal insufficiency (parts 1 and 2). These guidelines offer more information on micronutrients and parenteral nutrition but share in the limitation of how malnutrition is defined.

Other considerations

DRG codes are listed in Table X and Table XI, respectively.

Table X.

Diagnosis

ICD-10 Code

Kwashiorkor

E40

Marasmus

E41

Other severe protien calorie malnutrition

E46

Vitamin A deficiency

E50.9

Vitamin B deficiency, unspecified

E53.9

Vitamin C deficiency

E54

Vitamin D deficiency

E55.9

Other nutritional deficiencies

E56.8

Overweight and obesity

E66.3

Obesity

E66.9

Morbid obesity

E66.01

Table XI.

Diagnosis

DRG Code

Nutritional and miscellaneous metabolic disorders with major complications and comorbidities

640

Nutritional and miscellaneous metabolic disorders without major complications and comorbidities

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